Molecular control of animal cell cytokinesis

Fededa, Juan Pablo; Gerlich, Daniel W.

doi:10.1038/ncb2482

Cited by 295 publications

(303 citation statements)

References 141 publications

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“…Detection of the contractile ring provides evidence of cardiomyocyte cytokinesis. The contractile ring consists of regulatory and motor proteins (22), including the mitotic kinesin-like protein (MKLP-1), a component of the centralspindlin complex, which is required for completion of cytokinesis (23). We developed a cardiomyocyte cytokinesis assay by staining thick (30 μm) myocardial sections with antibodies against MKLP-1 and α-actinin (Fig.…”

Section: Resultsmentioning

confidence: 99%

Cardiomyocyte proliferation contributes to heart growth in young humans

Mollova¹,

Bersell

Walsh³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

647

578

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The human heart is believed to grow by enlargement but not proliferation of cardiomyocytes (heart muscle cells) during postnatal development. However, recent studies have shown that cardiomyocyte proliferation is a mechanism of cardiac growth and regeneration in animals. Combined with evidence for cardiomyocyte turnover in adult humans, this suggests that cardiomyocyte proliferation may play an unrecognized role during the period of developmental heart growth between birth and adolescence. We tested this hypothesis by examining the cellular growth mechanisms of the left ventricle on a set of healthy hearts from humans aged 0-59 y (n = 36). The percentages of cardiomyocytes in mitosis and cytokinesis were highest in infants, decreasing to low levels by 20 y. Although cardiomyocyte mitosis was detectable throughout life, cardiomyocyte cytokinesis was not evident after 20 y. Between the first year and 20 y of life, the number of cardiomyocytes in the left ventricle increased 3.4-fold, which was consistent with our predictions based on measured cardiomyocyte cell cycle activity. Our findings show that cardiomyocyte proliferation contributes to developmental heart growth in young humans. This suggests that children and adolescents may be able to regenerate myocardium, that abnormal cardiomyocyte proliferation may be involved in myocardial diseases that affect this population, and that these diseases might be treatable through stimulation of cardiomyocyte proliferation.heart failure | pediatrics H eart failure, a leading public health problem worldwide (1), is linked to the loss of cardiomyocytes (2-4). The only currently available, definitive therapy-heart transplantation-is limited by donor availability. New approaches, such as cell transplantation, have shown encouraging results in clinical trials (5, 6). However, a third, complementary strategy has emerged, based on stimulating endogenous regenerative mechanisms. One approach for developing such regeneration strategies is to examine the cellular mechanisms of myocardial growth, since mechanisms of regeneration should be similar to the mechanisms of development.Although stem and progenitor cells are important for morphogenesis of the myocardium, developmental growth in a number of nonhuman species is largely driven by cardiomyocyte proliferation (7-9). In biological models that, unlike adult humans, regenerate myocardium, cardiomyocyte proliferation is important for regeneration as well as postnatal heart growth (10, 11). For example, in mice, developmental cardiomyocyte proliferation continues for up to day 7 after birth, which coincides with the loss of regenerative capacity (11,12). The close temporal relationship between cardiomyocyte proliferation and heart regeneration in animals raises the question of whether and to what age and extent cardiomyocyte proliferation plays a role in humans. The answer may help us understand the endogenous regenerative potential of the human heart and possibly indicate strategies for stimulating cardiomyocyte proliferation to reg...

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Section: Resultsmentioning

confidence: 99%

Cardiomyocyte proliferation contributes to heart growth in young humans

Mollova¹,

Bersell

Walsh³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

647

578

View full text Add to dashboard Cite

show abstract

“…Over the last decades, genetic screens and RNAibased approaches have led to the identification of an array of conserved regulators of cytokinesis in animal cells (see Table 1) (Glotzer 2005;Eggert et al 2006;Fededa and Gerlich 2012;Green et al 2012). It is likely that few nonredundant, conserved, and critical regulators of cytokinesis remain to be discovered.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Cytokinesis in Animal Cells

D’Avino

Giansanti

Petronczki

2015

Cold Spring Harb Perspect Biol

182

226

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“…[1][2][3][4] Because of the highly stereotyped sequence of events that characterize this process and of the strong phylogenetic conservation of the underlying molecular machinery, 2,5 cytokinesis is currently considered a 'default' biological process, occurring similarly in the different cell types. However, it is well known that specialized proliferating cells are characterized by significant variations of the standard scheme, such as incomplete cytokinesis in trophoblast cells, hepatocytes, Purkinije neurons, cardiomyocytes 6 and spermatogonia 7 and asymmetric cytokinesis in meiotic oocytes and in cortical neuroepithelial precursors.…”

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confidence: 99%

Tissue-specific control of midbody microtubule stability by Citron kinase through modulation of TUBB3 phosphorylation

et al. 2015

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Cytokinesis, the physical separation of daughter cells at the end of cell cycle, is commonly considered a highly stereotyped phenomenon. However, in some specialized cells this process may involve specific molecular events that are still largely unknown. In mammals, loss of Citron-kinase (CIT-K) leads to massive cytokinesis failure and apoptosis only in neuronal progenitors and in male germ cells, resulting in severe microcephaly and testicular hypoplasia, but the reasons for this specificity are unknown. In this report we show that CIT-K modulates the stability of midbody microtubules and that the expression of tubulin β-III (TUBB3) is crucial for this phenotype. We observed that TUBB3 is expressed in proliferating CNS progenitors, with a pattern correlating with the susceptibility to CIT-K loss. More importantly, depletion of TUBB3 in CIT-K-dependent cells makes them resistant to CIT-K loss, whereas TUBB3 overexpression increases their sensitivity to CIT-K knockdown. The loss of CIT-K leads to a strong decrease in the phosphorylation of S444 on TUBB3, a post-translational modification associated with microtubule stabilization. CIT-K may promote this event by interacting with TUBB3 and by recruiting at the midbody casein kinase-2α (CK2α) that has previously been reported to phosphorylate the S444 residue. Indeed, CK2α is lost from the midbody in CIT-K-depleted cells. Moreover, expression of the nonphosphorylatable TUBB3 mutant S444A induces cytokinesis failure, whereas expression of the phospho-mimetic mutant S444D rescues the cytokinesis failure induced by both CIT-K and CK2α loss. Altogether, our findings reveal that expression of relatively low levels of TUBB3 in mitotic cells can be detrimental for their cytokinesis and underscore the importance of CIT-K in counteracting this event.

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Molecular control of animal cell cytokinesis

Cited by 295 publications

References 141 publications

Cardiomyocyte proliferation contributes to heart growth in young humans

Cardiomyocyte proliferation contributes to heart growth in young humans

Cytokinesis in Animal Cells

Tissue-specific control of midbody microtubule stability by Citron kinase through modulation of TUBB3 phosphorylation

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